A new approach to cancer immunochemotherapy is proposd which is particularly appropriate for treatment of metastasizing tumors. Tumor cell-directed liposomes will be used to home chemotherapeutic agents to the tumor target cells. Materials that are enclosed inside liposomes are protected from metabolic degradation and may be selectively concentrated in target cells. Encapsulated agents also may exhibit less systemic toxicity than the free drugs. Homing will be accomplished by attaching antitumor cell antibodies on the exterior of the liposomes. Specific rabbit anti-guinea pig tumor antibodies will be prepared toward the weakly antigenic, syngeneic strain 2 guinea pig line-10 hepatocarcinoma cells. Syngeneic line-1 hepatocarcinoma cells will be utilized as a control for efficacy and specificity. Tumoricidal effects in vitro will be determined primarily by the 51Cr release microcytotoxicity assay. Efficacy in vivo will be tested by various means, including injection of target-directed liposomes (a) together with tumor cells or (b) directly into established tumor nodules or (c) systemically after surgical excision of the primary tumor. Our in vitro experiments demonstrate that liposomes containing both anti-line-10 antibody and actinomycin D specifically home to and kill line-10 tumor cells. This model should be particularly useful in determining the potential for target-directed liposomes in the prevention and cure of tumors metastasizing to regional lymph nodes.